Objective: To investigate the therapeutic effect of bone marrow mesenchymal stem cells ( BMSCs) mod- ified by bone morphogenetic protein ( BMP) -2 gene combined with nano-hydroxyapatite ( nHA) / polyamide 66 ( PA66) on femoral nonunion in rats． Methods : Rat BMSCs were isolated and divided into the stent + BMSCs group，stent + BMSCs + rhBMP-2 group，and stent + BMSCs + Ad-BMP-2 group; human recombinant BMP-2 ( rh- BMP-2) or adenovirus-infected BMP-2 ( Ad-BMP-2) vector was transfected into BMSCs and loaded onto nHA / PA66 stent materials．Flow cytometry was used to detect that BMSCs expressed specific surface markers．Cell pro- liferation was detected by MTT assay，related bioactive factors［platelet-derived growth factor ( PDGF) ，transfor- ming growth factor-β ( TGF-β) ，vascular endothelial growth factor ( VEGF) ，fibroblast growth factor ( FGF) ，os- teocalcin ( OCN) ，osteonectin ( ON) ］were detected by ELISA，alkaline phosphatase ( ALP) activity was detec- ted，and cell growth and adhesion were observed by scanning electron microscopy ( SEM) ．In the atrophic nonun- ion model of SD rats，the stent + BMSCs + rhBMP-2 or stent + BMSCs + Ad-BMP-2 complex was implanted into the defect area，which was divided into the rhBMP-2 group and the Ad-BMP-2 group，and the therapeutic effect was e- valuated by X-ray and MicroCT． Results: The surface of the nHA / PA66 stent was smooth and porous，and BMSCs adhered well．Flow cytometry showed high expression of CD29 and CD90 and low expression of CD45 and CD34 in BMSCs．MTT showed that the cells proliferated rapidly after 72 h．Compared with the stent + BMSCs group and the stent + BMSCs + rhBMP-2 group，the ALP activity，the expressions of PDGF，TGF-β , VEGF，FGF，OCN，and ON in the stent + BMSCs + Ad-BMP-2 group were significantly up-regulated ( P＜0. 05) ．12 weeks after surgery， the stent complex in the Ad-BMP-2 group of rats was completely wrapped by newly formed cortical bone，and the surface was smooth and intact．X-ray showed that the complex in the Ad-BMP-2 group was completely wrapped by newly formed cortical bone，and the recovery degree was better than that in the rhBMP-2 group．Micro-CT results showed that compared with the rhBMP-2 group，the bone volume fraction，trabecular thickness，trabecular num- ber，bone mineral density，and bone mineral content in the Ad-BMP-2 group all increased 12 weeks after surgery ( P＜0. 05) ，and the trabecular separation level decreased ( P＜0. 05) ． Conclusion Ad-BMP-2-transfected BM- SCs combined with nHA / PA66 stent material can express bioactivity more effectively，provide a continuous and good microenvironment for the proliferation and differentiation of BMSCs，which is beneficial to promoting local os- teogenic activity and bone defect repair．

Objective To explore the effects of individual or combination medication of epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)combined with chemotherapy on progres-sion-free survival(PFS)in advanced non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutation.Methods A total of 110 advanced NSCLC patients with EGFR mutation in our hospital from January 2019 to April 2021 were selected as research objects.Ac-cording to different therapeutic plans,they were divided into group A with 37 cases(anlotinib chemo-therapy),group B with 32 cases(icotinib chemotherapy)and group C with 41 cases(anlotinib plus icotinib and chemotherapy).The short-term effect,levels of vascular growth factors before and after treatment,and the incidence of adverse reactions were compared among the three groups.After 2 years of follow-up,survival curve was drawn by Kaplan-Meier method,and survival rate and PFS were compared in three groups by Log-rank.Results The objective response rate(ORR)was 68.29％in the group C,which was significantly higher than 43.24％in the group A and 40.62％in the group B(P＜0.05);after treatment,levels of serum vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF)and platelet-derived growth factor(PDGF)in the group C were significantly lower than those in the group A and the group B(P＜0.05);the total incidence of adverse reac-tions was 29.27％in the group C,which showed no significant differences when compared to 24.32％in the group A and 25.00％in the group B(P＞0.05).By the time of the last follow-up,the 2-year overall survival rate was 74.29％in the group C,which was significantly higher than 51.09％in the group A and 45.03％in the group B(Log-rank x2=6.478,P=0.039);the medi-an PFS in the group A,the group B and the group C was 9.0,8.6 and 13.2 months respectively,and differences were statistically significant(Log-rank x2=6.264,P=0.043).Conclusion For the advanced NSCLC patients with EGFR mutations,combination medication of EGFR-TKI com-bined with chemotherapy can effectively increase ORR,reduce levels of serum vascular growth fac-tors,prolong the PFS,and the safety is good.

Objective To explore the effects of individual or combination medication of epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)combined with chemotherapy on progres-sion-free survival(PFS)in advanced non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutation.Methods A total of 110 advanced NSCLC patients with EGFR mutation in our hospital from January 2019 to April 2021 were selected as research objects.Ac-cording to different therapeutic plans,they were divided into group A with 37 cases(anlotinib chemo-therapy),group B with 32 cases(icotinib chemotherapy)and group C with 41 cases(anlotinib plus icotinib and chemotherapy).The short-term effect,levels of vascular growth factors before and after treatment,and the incidence of adverse reactions were compared among the three groups.After 2 years of follow-up,survival curve was drawn by Kaplan-Meier method,and survival rate and PFS were compared in three groups by Log-rank.Results The objective response rate(ORR)was 68.29％in the group C,which was significantly higher than 43.24％in the group A and 40.62％in the group B(P＜0.05);after treatment,levels of serum vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF)and platelet-derived growth factor(PDGF)in the group C were significantly lower than those in the group A and the group B(P＜0.05);the total incidence of adverse reac-tions was 29.27％in the group C,which showed no significant differences when compared to 24.32％in the group A and 25.00％in the group B(P＞0.05).By the time of the last follow-up,the 2-year overall survival rate was 74.29％in the group C,which was significantly higher than 51.09％in the group A and 45.03％in the group B(Log-rank x2=6.478,P=0.039);the medi-an PFS in the group A,the group B and the group C was 9.0,8.6 and 13.2 months respectively,and differences were statistically significant(Log-rank x2=6.264,P=0.043).Conclusion For the advanced NSCLC patients with EGFR mutations,combination medication of EGFR-TKI com-bined with chemotherapy can effectively increase ORR,reduce levels of serum vascular growth fac-tors,prolong the PFS,and the safety is good.

Objective: To observe the effects of nootkatone on depression-like behavior, neurogenesis and protein kinase A(PKA)/cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF) signaling pathway in hippocampus of chronic unpredictable stress(CUS) treated mice, and to explore the role and molecular mechanism of nootkatone′s antidepressant effect. Methods: Male C57 BL/6 mice were randomly divided into 3 groups: the control group(saline), the CUS group(CUS+saline), the CUS+nootkatone group(CUS+nootkatone). The sucrose preference test and forced swim test were used to evaluate the depression-like behaviors. The mRNA expression of BDNF in hippocampus was measured by RTPCR. The expression levels of BDNF, PKA and phosphorylated cyclic adenosine monophosphate response element-binding protein(p-CREB) in hippocampus were determined by Western blot. The level of neurogenesis was measured by immunofluorescence. Results: Compared with the control group, the sucrose preference decreased(P<0.05) and the latency decreased(P<0.05), and immobility time increased in forced swim test(P<0.05) in CUS group, the expression levels of BDNF mRNA(P<0.05) and protein(P<0.05), PKA(P<0.05) and p-CREB(P<0.05) decreased. The sucrose preference of the CUS+nootkatone group increased(P<0.05) and the latency increased(P<0.05), and immobility time decreased in forced swim test(P<0.05), the expression levels of BDNF mRNA(P<0.05) and protein(P<0.05), PKA(P<0.05) and p-CREB(P<0.05) increased in comparison with the CUS group. Compared with control group, the number of hippocampal doublecortin(DCX) labeled neurons decreased(P<0.05) in CUS group. Compared with the CUS group, the number of DCX labeled neurons increased in the CUS+nootkatone group(P<0.05). Conclusion The improvement of depressive symptoms in CUS mice by nootkatone may be related to the neurogenesis in dentate gyrus of hippocampus and the activation of PKA/CREB/BDNF signaling pathway.

Heterotopic pregnancies are rare and difficult to be diagnosed early. A patient with combined intrauterine pregnancy and cervical pregnancy was admitted in Qingdao Municipal Hospital in 2019. The patient complained of abnormal vaginal bleeding after menopause and was misdiagnosed as simple intrauterine pregnancy. She underwent artificial abortion and suffered intraoperative hemorrhage. To stop bleeding, she received the treatment of uterine artery embolization immediately. Afterwards, cervical residual pregnancy tissues started necrosis, blood β-human chorionic gonadotropin level and the cervix appearance gradually returned to normal. This report suggests that cervical heterotopic pregnancy inclines to be mis diagnosed. Correct diagnosis should be made as soon as possible. Selective uterine artery embolization is an effective measure to prevent and treat massive bleeding.
Chorionic Gonadotropin, beta Subunit, Human ; Female ; Humans ; Pregnancy ; Pregnancy, Heterotopic/surgery* ; Uterine Artery Embolization ; Uterine Hemorrhage

Objective:To investigate the current situation of general practitioners' occupational pressure in Heilongjiang Province, and explore its relationship with professional identity and perceived organizational support. It aims to provide references for the construction of general practitioners and the development of general medical education.Methods:The general situation questionnaire, perceived organizational support scale, occupational pressure scale, and professional identity scale were applied through network and site surveys for collecting data. A total of 288 questionnaires were collected with 263 valid questionnaires (91.3%). Pearson correction analysis and bootstrap analysis were performed for data analysis.Results:The average score of occupational pressure among general practitioners was (115.95±22.40), and the results of Pearson correction analysis showed that perceived organizational support was negatively correlated with occupational pressure ( r=-0.413, P<0.01) and positive correlation with professional identity ( r=0.587, P<0.01). There were also significant negative correlations between professional identity and occupational pressure ( r=-0.442, P<0.01). Moreover, the mediating effect showed that professional identity had a certain mediating effect on the relationship between perceived organizational support and occupational pressure (LLCI=-0.2039, ULCI=-0.0760, P<0.05). Conclusion:General practitioners' occupational pressure was at a high level, which can be reduced through improving the perceived organizational support and professional identity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

Objective: To analyze the infection composition and drug resistance to Gram-negative (G^-) bacilli in children′s respiratory tract in Suzhou, in order to provide evidence for rational use of antibiotics clinically. Methods: G^- bacilli culture samples were collected from 21 561 cases of nasopharyngeal secretions from patients with respiratory tract infection admitted at the Department of Respiratory, Children′s Hospital of Soochow University from January 2007 to December 2016, including 21 246 cases in general wards, and 315 patients who were transferred to the respiratory department after treatment in the Intensive Care Unit(ICU), and the children were divided into the general ward group and the ICU group, and the pathogens were compared and the changes in bacterial susceptibility were dynamically observed between the 2 groups. Results: The primary G^-bacteria for respiratory infection was Haemophilus influenzae, followed by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii.The detection rates of Klebsiella pneumoniae and Pseudomonas aeruginosa in the ICU group were 16.8% (21/125 strains)and 14.4%(18/125 strains), respectively, which were significantly higher than those in the general ward group [10.0%(208/2 071 strains), 9.2%(190/2 071 strains)]. The detection rates of G^-bacteria in the ICU group were 33.7%(106/315 cases), which were significantly higher than those in the general ward group [9.4%(1 997/21 246 cases)], and the difference was statistically significant(χ²=210.325, P<0.001). The rare G^-bacillus such as Stenotrophomonas maltophilia, Acinetobacter junii and Burkholderia onion were higher in the ICU group [17.6%(22/125 strains)] than that in the general ward group [6.4% (132/2 071 strains)]. The rate that of G^-bacteria with two or more mixed infection in ICU group [17.0% (18/106 cases)] was significantly higher than in the general ward group [3.4%(68/1 997 cases)], and the difference was statistically significant(χ²=47.3, P<0.05). For the mixed infection, the ICU group was mainly composed of Klebsiella pneumoniae mixed with Pseudomonas aeruginosa or Escherichia coli, while the general ward group was composed of Haemophilus influenzae mixed with Pseudomonas aeruginosa or Escherichia coli.The sensitivity of Haemophilus influenzae to Ampicillin, Sultamicillin, Cefuroxime, Cefaclor and Azithromycin decreased, and the sensitivity to Chloramphenicol, Tetracycline and Trimethoprim+ Sulfamethoxazole increased year by year, and there were statistically significant differences in different years (all P<0.05). The sensiti-vity to Escherichia coli to Ceftazidime decreased year by year, and the sensitivity to Ampicillin and Levofloxacin increased year by year, and there were statistically significant differences in different years (all P<0.05). The sensitivity to Klebsiella pneumoniae to Cefoperazone/Sulbactam and imipenem decreased, and the sensitivity to Ciprofloxacin and Levofloxacin increased, and there were statistically significant differences in different years (all P<0.05). The sensitivity to Pseudomonas aeruginosa, Cefoperazone/Sulbactam and Ceftriaxone decreased year by year, and the sensitivity to Levofloxacin increased, and there were statistically significant differences in different years (all P<0.05). The detection rate of carbapenem-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa showed an increasing trend, and there were statistically significant differences in different years (all P<0.05). Conclusions The primary G^-bacteria for respiratory infections is Haemophilus influenzae, G^-bacilli especially, the mixed infection of G^-bacilli, is more likely to cause severe and critical respiratory infections.The resistance rate of G^-bacteria infection in children′s respiratory tract to commonly used antibiotics is generally on the rise.

As an important zoonotic pathogen, Staphylococcus aureus has led to serious mastitis and endometritis in infected dairy cows. In this study, a total of 164 strains of S. aureus were isolated from dairy cows in Xinjiang Province, China, and subjected to assays to determine drug susceptibility and biofilm (BF) formation ability. Enterotoxin-related genes were detected, and the transcription levels of genes related to BF formation were determined by using reverse transcription-quantitative polymerase chain reaction. Moreover, the pathogenicity of isolates with different BF formation abilities was determined by measuring their hemolysis activity, half lethal dose (LD₅₀) and organ bacterial load. The results showed that 86.0% of S. aureus isolates could form BF. Among them, 42.1% of the strains had weak BF formation ability, and most strains with a strong BF formation ability were ica gene carriers. The S. aureus isolates displayed multidrug resistance and their drug resistance was positively correlated with their BF formation ability. Moreover, 96.3% of the S. aureus isolates carried enterotoxin genes. Among them, the detection rates of the novel enterotoxin genes were higher than those of conventional enterotoxin genes. Furthermore, isolates with a strong BF formation ability had higher LD50 but lower hemolysis ability and organ bacterial load than those of the isolates with weak or no BF ability. However, isolates without BF ability produced more severe pathological changes than those of isolates with strong BF formation ability. These findings suggest that higher BF ability and presence of novel enterotoxin genes are important characteristics of S. aureus isolates from dairy cows in Xinjiang Province, China, and such isolates may pose potential threats to food safety.
Bacterial Load ; Biofilms ; China ; Drug Resistance ; Drug Resistance, Microbial ; Drug Resistance, Multiple ; Endometritis ; Enterotoxins ; Female ; Food Safety ; Hemolysis ; Lethal Dose 50 ; Mastitis ; Polymerase Chain Reaction ; Staphylococcus aureus ; Staphylococcus ; Virulence

Xin'an doctor discussed acupuncture and moxibustion on ' and , calling it "orthodox needling method". 's academic thoughts on moxibustion were mainly reflected in () and (). made an incisive exposition of moxibustion treatment of heat syndrome, ulcer and other issues, and there is a corresponding test case for mutual reference. He believed that the moxibustion method only adapts to sick patients and holds opposition to moth moxibustion care for those who were disease-free; he also advocated that detailed verification of different syndrome should be conducted before acupuncture. This paper expounds 's academic thoughts on moxibustion can be used for heat syndrome, moxibustion does not stay phlegm, moxibustion need syndrome and moxibustion treatment of ulcer. It is believed that can present his own unique insights on the basis of his successors. He had played a guiding and promoting role in the development of academic theory of moxibustion.